Estrogen receptors (ER) were assayed on hepatocellular carcinoma (HCC) and surrounding liver tissue in 30 adult patients. All specimens were obtained at the time of surgery. Cirrhosis of the liver was associated with 28 patients and chronic hepatitis in 2 patients. ERs were detected in 12 of 30 HCCs. The value ranged from 1.4 to 9.2 fmol/mg cytosol protein with the dissociation constant (Kd) value less than 1 nanomol. On the other hand, 13 of 28 cirrhotic livers had measurable amounts of the receptors that ranged from 1.5 to 4.1 fmol/mg cytosol protein. Two livers with chronic hepatitis did not have detectable amounts of ERs. The receptors were not detected in both the tumor and liver in ten patients. The ER titers in HCC did not have any correlation with serum levels of α-fetoprotein or carcinoembryonic antigen, hepatitis B virus profils, and histologic types of the tumor. In the light of the current results, it would be of great interest whether hormone therapy can be used or not as a treatment of naturally occurring HCC in humans.